T011 Influence of anti-Parkinson’s disease drugs on the neuro-plasticity induced by quadripulse transcranial magnetic stimulation (QPS)

Abstract

The relation between plasticity and dopamine has been recently investigated by several investigators. L-dopa enhanced bidirectional synaptic plasticity in the primary motor cortex (M1) of the human brain. Abnormally reduced plasticity was normalized by L-dopa in Parkinson’s disease (PD) patients. Some clinical symptoms significantly correlated with the plasticity abnormalities. Other anti-Parkinson’s disease drugs may have some influence on the cortical plasticity. We studied how anti-Parkinson’s disease drugs modulate the LTP induced by quadripulse transcranial magnetic stimulation (QPS) in the human brain. L-dopa enhanced both LTP and LTD in normal volunteers. In contrast, pramipexole have no influence on either LTP or Ltd. Zonisamide (ZNS) (25 ms) tended to enhance LTP in aged healthy volunteers in total. In the aged group, 10 in 24 volunteers were non-responders, defined as those whose average MEP ratio was equal or less than 1. ZNS significantly enhanced the plasticity in 10 non-responders. A single-dose of caffeine (200 mg), which inhibits both adenosine A 1 and A 2A receptors, significantly reduced LTP in the responders (4 in 12 healthy young volunteers). A new anti-Parkinson’s disease drug (Istradefylline), adenosine A2A receptor antagonist also decreased LTP. Based on our results and basic knowledge about the dopamine innervation of the primary motor cortex, we conclude that the motor cortical plasticity studied by QPS over M1 must be influenced by D1 projection from ventral tegmentum area to M1. This plasticity evaluation by QPS may reflect some symptoms in PD patients.